Study Reveals Key to Promoting Lifelong Health: Discovery of Cellular Aging Trigger

Keiko Kono envisions a future where individuals remain healthy until their last day.

Her latest research, which demonstrates that cell membrane damage accelerates cell aging, could provide a roadmap for scientists globally to achieve this goal.

Traditionally, mechanical damage to the cell membrane was thought to result in two possible cellular outcomes: recovery or death. However, Ms. Kono’s study unveiled a third outcome—cellular senescence, or cell aging.

“Initially, my goal was not related to aging or any similar topic. I simply aimed to address a fundamental question: how do our cells repair membrane damage,” stated Ms. Kono. “Ultimately, we discovered that cell membrane damage, to some extent, alters cell fate.”

Related Stories

Ms. Kono and her team studied budding yeast and normal human fibroblasts, which are fibrous materials supporting and connecting other tissues or organs.

According to Ms. Kono, the decisive factors in determining cell fate are the degree of damage and subsequent influx of calcium ions, which may regulate cell excitability, neurotransmitter release, or gene transcription.

Cellular senescence plays a role in myriad processes throughout the body, including wound healing, cell division, and cell proliferation. Prolonged senescence, however, can have adverse effects and contribute to cancer, DNA damage, altered gene functionality, and age-related illnesses.

With each breakthrough, researchers gain additional tools in the ongoing battle against aging. “Science is akin to constructing a pyramid. We are merely placing one block at the foundation,” shared Ms. Kono. “That’s what I’m doing, and scientists globally—regardless of their location—will read it, add another block, and watch the pyramid rise, with someone eventually developing a drug that enhances longevity and health. That’s my aspiration.”

Although significant progress has been made in senescence research, researchers have faced challenges due to the lack of reliable methods for identifying senescence. Their study involved using nuclear morphology features of senescent cells to create machine-learning classifiers that accurately predicted senescence induced by various stressors in diverse cell types and tissues.

They employed senescence “classifiers” to characterize drugs that eliminate senescent cells, known as senolytics, or screen for drugs that induce senescence specifically in cancer cells while sparing normal cells.

“Almost every cell type can transition into a senescent state, but delineating what senescence manifests as at the cellular level and establishing a standardized method to identify it across thousands of cell types have been challenging,” stated the authors in their press release.

With recent advances in machine learning and AI, researchers at the LMS have managed to analyze senescence hallmarks to confirm the presence of senescent cells. They have also demonstrated the adaptability of their algorithms to work with lab-grown cells for research purposes and to analyze tissue samples obtained from mouse livers and individuals with fatty liver disease.

Senescent cells have become a focal point for researchers worldwide in both anti-cancer and anti-aging endeavors. “Initial studies in animal models have shown that life and health spans are extended when subjects are treated with ‘senolytic’ medications that target and eradicate senescent cells,” as stated by the researchers in the press release.

In what they termed “a new era of senolytic therapies,” the study authors revealed that their senescence classifiers could be employed to identify senolytics or selectively prompt senescence in cancer cells in laboratory experiments. This tool also permitted them to evaluate over 600 drugs for senolytic properties, uncovering several potential new therapeutic agents.

Delaying Cell Aging

Ms. Kono believes that achieving longer, healthier lives is a distinct possibility in the near future. “Typically, this would take 30 or 40 years to accomplish, but aging research has progressed rapidly in recent times,” she noted. “Many talented individuals are devoted to it. Consequently, I genuinely believe that within 10 or 15 years, we might develop a drug or supplement that can genuinely extend healthy human lives on Earth.”

While acknowledging that humans will inevitably die, Ms. Kono encourages hope for a life free of incurable, agonizing illnesses until the end. “We can aspire to a healthy longevity. This research won’t grant you a lifespan of 400 or 500 years. We aren’t pursuing that. The goal of our research is to maintain good health until the end of life.”

Ms. Kono likened the ideal outcome to stories of elderly individuals who simply feel tired and lay down, peacefully passing away shortly after.

Ms. Kono explained that various mechanisms contribute to the naked mole-rat’s longevity and excellent health, and she aims to delve deeper into this topic. “They possess a more robust DNA repair mechanism. Additionally, their senescent or aging cells do not accumulate in their bodies.” She speculated that their cells may possess better protection and experience less damage.

Initially, research focused on eliminating senescent cells, which could lead to side effects, Ms. Kono pointed out. Instead, she proposes concentrating on preventing mechanical damage to slow down the generation of senescent cells. “By doing so, you can prolong your health. Ultimately, that is the direction I am taking.”